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1.
Talanta ; 233: 122535, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215038

RESUMO

Bacterial infection poses a serious threat to human health worldwide. Rapid antimicrobial susceptibility testing (AST) is essential for the clinical treatment of bacterial infection patients. However, the traditional AST relies on bacteria culture, which is time-consuming and limits the analysis to culturable species. Herein, we present a laser desorption ionization (LDI) mass spectrometry-based method for rapid bacterial viability assessment and AST by tracing the redox of resazurin (RS) by viable bacteria. RS as well as its reduction product, fluorescent resorufin (RF), can be directly detected by LDI-MS in the absence of matrix. The intensity ratio between RF and RS can be used to assess the viability of bacteria in specimens. We have demonstrated the high efficiency of the method using different bacterial species, including K. pneumoniae, S. aureus, E. coli, and P. aeruginosa, and various antibiotic drugs, such as ciprofloxacin, ampicillin, tetracycline, oxytetracycline, ciprofloxacin and levofloxacin. Compared to traditional methods based on optical absorption, the current method is faster and more sensitive. Furthermore, we applied the method to bacterial viability detection and AST using human body fluid samples, i.e. serum and urine, demonstrating that it can screen rapidly appropriate antibiotic drugs for timely clinical treatment of infectious diseases. With the advantages of simplicity in methodology as well as sensitivity and speed in analysis, the current method holds the potential of clinical usages.


Assuntos
Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Humanos , Lasers , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
2.
Mymensingh Med J ; 30(3): 625-632, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226447

RESUMO

The aim of this study was to find the prevalence of ESBL genes among A. baumannii isolates. In this cross sectional study, 49 Acinetobacter spp. were isolated from various clinical samples from March 2019 to February 2020 conducted in the department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh. Clinical samples including endotracheal aspirates, wound swab/pus, urine and blood. A total of 380 samples were analyzed. Growth was obtained in 34.21% of the samples yielding 130 organisms. Out of 130 organisms, 49(37.69%) were Acinetobacter spp. Among 49 Acinetobacter spp, 39(79.59%) were Acinetobacter baumannii which was identified by PCR targeting OXA-51 like gene. Amplification of the ESBL encoding genes, namely CTX-M, TEM, SHV done by molecular technique PCR. The most antibacterial resistance was against ceftriaxone (79.48%) and lower resistance only showed in colistin (12.82%). All the isolates were sensitive to tigecycline. The distribution of ESBLs genes such as TEM 20(51.28%), CTX-M 16(41.02%) and SHV 0(0%). The high resistance to most of the antibiotics among the studied strains and also a high prevalence of TEM gene in A. baumannii strains found in our study gives alarming sign towards the treatment complexity of these strains.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Bangladesh/epidemiologia , Estudos Transversais , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Centros de Atenção Terciária , beta-Lactamases/genética
3.
Mymensingh Med J ; 30(3): 725-737, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34226462

RESUMO

Multi-drug resistant Typhoid fever (resistant to previously used chloramphenicol, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole) has been commonly described in the South East Asia region and a recent report suggests that the salmonella typhi have reduced response to fluoroquinolones (nalidixic acid-resistant). The optimum treatment protocol for this type of serovar has not been established. This study compared different antimicrobial regimens for the treatment of uncomplicated typhoid fever which was conducted in the medicine ward of Dhaka Medical College Hospital (DMCH) and outdoor setting in private practice in Dhaka metropolitan city, Mymensingh and Sylhet town from January 2017 to December 2017. Bangladeshi adults with uncomplicated typhoid fever were included in this an open-label randomized controlled trial. Ciprofloxacin (20mg/kg of body weight/day for 14 days), azithromycin (20mg/kg/day for 14 days), and Cefixime (16mg/kg/day for 14 days) were compared. Of the 81 enrolled patients, 62 were eligible for analysis (61 S. enterica serovar Typhi, 1 Salmonella enterica serovar paratyphi A). Of the S enterica serovar Typhi isolates, 88.7% (55/62) were MDR and 93.5% (58/62) were nalidixic acid resistant (NAR). The clinical cure rate was 62% (13/21) with ciprofloxacin, 71% (15/21) with Cefixime, and 85% (17/20) with azithromycin (p=0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with cefixime (7.1 days [6.2 to 8.1 days]) and ciprofloxacin (8.2 days [7.2 to 9.2 days]) (p<0.001). All three antibiotics were well tolerated. A 7-day course of azithromycin can be successfully used in uncomplicated typhoid fever due to isolates of MDR S enterica serovar Typhi.


Assuntos
Azitromicina , Febre Tifoide , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Bangladesh/epidemiologia , Cefixima/uso terapêutico , Ciprofloxacina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia
4.
Molecules ; 26(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201372

RESUMO

A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED50) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Nitrofenóis/farmacologia , Piperazina/farmacologia , Compostos Policíclicos/farmacologia , Animais , Linhagem Celular , Insetos/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana/métodos , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
5.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208294

RESUMO

Cryptococcus neoformans is a facultative intracellular pathogen responsible for fungal meningoencephalitis primarily in immunocompromised individuals. It has become evident the pathogenicity of C. neoformans is dependent on the fungal cell's environment. The differential expression of virulence factors, based on the cell's environmental conditions, is one mechanism allowing for the environmental control of the pathogenic ability of C. neoformans. Here, we discuss how these virulence factors (including melanin, the polysaccharide capsule, and Antiphagocytic protein 1) have been shown to be differentially expressed dependent on the cell's environment. The genetics and signaling pathways leading to the environmental-dependent regulation of virulence factors will also be examined. Susceptibility to antifungal therapeutics is also regulated by the environment, and thus affects the pathogenic abilities of C. neoformans and disease outcomes. This review will also examine the role of the C. neoformans's environment on antifungal susceptibilities, and the genetics and signaling pathways responsible for these susceptibility alterations. By examining the complex interplay between the environment and the pathogenicity of C. neoformans, we have a better understanding of the intricacies of the pathogen-environment interaction and how to exploit this interaction to develop the most effective treatment protocols.


Assuntos
Antifúngicos/farmacologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/patogenicidade , Meio Ambiente , Fatores de Virulência/metabolismo , Animais , Humanos , Pulmão/microbiologia , Testes de Sensibilidade Microbiana
6.
BMC Genomics ; 22(1): 530, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247587

RESUMO

BACKGROUND: Acinetobacter baumannii is a common nosocomial pathogen that poses a huge threat to global health. Owing to the severity of A. baumannii infections, it became necessary to investigate the epidemiological characteristics of A. baumannii in Chinese hospitals and find the reasons for the high antibiotic resistance rate and mortality. This study aimed to investigate the epidemiologic and genetic characteristics of A. baumannii isolated from patients with hospital acquired pneumonia (HAP), bloodstream infection (BSI) and urinary tract infection (UTI) in China and uncover potential mechanisms for multi-drug resistance and virulence characteristics of A. baumannii isolates. RESULTS: All isolates were classified into two primary clades in core gene-based phylogenetic relationship. Clonal complex 208 (CC208) mainly consisted of ST195 (32 %) and ST208 (24.6 %). CC208 and non-CC208 isolates had carbapenem resistance rates of 96.2 and 9.1 %, respectively. Core genes were enriched in 'Amino acid transport and metabolism', 'Translation', 'Energy production and conversion', 'Transcription', 'Inorganic ion transport and metabolism' and 'Cell wall/membrane/envelope synthesis'. Most isolates possessed virulence factors related to polysaccharide biosynthesis, capsular polysaccharide synthesis and motility. Eleven isolates belong to ST369 or ST191 (oxford scheme) all had the virulence factor cap8E and it had a higher positive rate in UTI (35.3 %) than in BSI (18.9 %) and HAP (12.9 %). ABGRI1 antibiotic resistance islands were responsible for streptomycin, tetracycline and sulfonate resistance. The blaOXA-23 gene was the most probable cause for carbapenem resistance, although the blaOXA-66 gene with nonsynonymous SNPs (F82L, I129L) was not. CONCLUSIONS: A. baumannii is a genomically variable pathogen that has the potential to cause a range of infectious diseases. There is high proportion of carbapenem resistance in isolates from all three infection sites (HAP, BSI and UTI), which can be attributed to the blaOXA-23 gene. CC208 is the predominant clone in blaOXA-23-carrying A. baumannii that should be monitored. Virulence factors involving bacteria motility and polysaccharide biosynthesis which are widespread in clinical A. baumannii strains deserve our attention.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Doenças Transmissíveis , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana Múltipla , Genômica , Humanos , Testes de Sensibilidade Microbiana , Filogenia , beta-Lactamases/genética
7.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205355

RESUMO

Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.


Assuntos
Acetofenonas/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Percepção de Quorum/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/efeitos dos fármacos , Piocianina/farmacologia
8.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198513

RESUMO

BACKGROUND: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. METHODS: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. RESULTS: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. CONCLUSIONS: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.


Assuntos
Antibacterianos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/fisiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Imunossupressão , Espaço Intracelular/microbiologia , Lipoglicopeptídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1
9.
J Agric Food Chem ; 69(28): 7831-7840, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34228443

RESUMO

Natural berberine-hybridized benzimidazoles as potential antibacterial agents were constructed to treat Staphylococcus aureus infection in the livestock industry. Bioassay showed that some new berberine-benzimidazole hybrids exhibited potent antibacterial efficacies, especially, the 2,4-dichlorobenzyl derivative 7d not only showed strong activity against S. aureus ATCC 29213 with the MIC value of 0.006 mM but also effectively eradicated bacterial biofilm and exhibited low toxicity toward mammalian cells. The drug combination experiments showed that compound 7d together with norfloxacin could enhance the antibacterial efficacy. Moreover, the 2,4-dichlorobenzyl derivative 7d did not show obvious propensity to develop bacterial resistance. Preliminary mechanism studies revealed that the active molecule 7d could damage the membrane integrity, stimulate ROS generation, and bind with DNA as well as S. aureus sortase A, thus exerting powerful antibacterial ability. In light of these facts, berberine-benzimidazole hybrid 7d showed a large potentiality as a new bactericide for treating S. aureus in the livestock industry.


Assuntos
Berberina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Benzimidazóis/farmacologia , Berberina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus aureus
10.
Environ Monit Assess ; 193(8): 497, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34286386

RESUMO

In the present work, leaf extract of Boswellia sacra was used as reductant for synthesis of silver nanoparticles (AgNPs). The variables such as volume of Boswellia sacra leaf extract (1%), volume of silver nitrate (1 mM), and temperature were optimized by response surface methodology via Box-Behnken design for the synthesis of AgNPs. Design-Expert software generated the optimum conditions for the highest yield of silver nanoparticles as 8 mL of 1 mM AgNO3, 8 mL of 1% Boswellia sacra leaf extract, and temperature = 55 °C. The formed AgNPs were isolated and purified by centrifugation process using ethanol/ distilled water. AgNPs were characterized using FTIR, SEM, TEM, EDX, and XRD. AgNPs showed surface plasmon resonance absorption band at 422 nm. XRD pattern indicated the crystalline nature of the particles (diameter 11.17 to 37.50 nm) with face-centered cubic structure. SEM and TEM images highlighted the formation of spherical AgNPs. The energy dispersive spectroscopic spectrum confirmed the presence of elemental silver. The microbial activity of AgNPs was evaluated against bacteria and fungi. Synthesized AgNPs were very effective against Gram-positive E. coli bacterial strains and fungal strains (Penicillium chrysogenum).


Assuntos
Boswellia , Nanopartículas Metálicas , Antibacterianos , Monitoramento Ambiental , Escherichia coli , Testes de Sensibilidade Microbiana , Extratos Vegetais , Prata
11.
Appl Microbiol Biotechnol ; 105(13): 5589-5605, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34196746

RESUMO

Global burden of fungal infections and associated health risk has accelerated at an incredible pace and needs to be attended at the earliest with an unbeatable therapeutic intervention. Candida glabrata is clinically the most relevant and least drug susceptible Candida species. In the pursuit of mining alternative novel drug candidates, the antifungal activity of a monoterpene phytoactive molecule geraniol (GR) against C. glabrata biofilm was evaluated. Biofilm inhibitory and eradication ability of GR evaluated against C. glabrata along with its clinical isolates. Impact of GR on various cellular pathways was evaluated to delineate its antifungal mode of action. GR has inhibited both planktonic and sessile growth of all the studied C. glabrata strains and eradicated the mature biofilm. GR reduced the carbohydrate and eDNA content, as well as hydrolytic enzyme activity in extracellular matrix of C. glabrata. The chemical profiling, microscopic, and spectroscopic studies revealed that GR targets chitin and ß-glucan in cell wall. Further, results highlighted the reduction of cell membrane ergosterol content, and blocking of ABC drug efflux pump by GR which was also confirmed by RT-PCR where expression of CDR1 and ERG4 was downregulated in GR exposed C. glabrata cells. The fluorescence microscopy and flow cytometry results emphasized the alteration in mitochondrial activity, increased Ca+2 uptake, thus changing the membrane permeability ensuing increased cytochrome C release from mitochondria to cytoplasm. Indeed, GR also has arrested cell cycle in G1/S phase and interfered with DNA replication. These observations suggest GR targets multiple cellular pathways and mediated killing of C. glabrata cells via apoptosis. In conclusion, the present study strengthens the candidacy of GR as novel antifungal therapeutic. Key points • GR inhibits growth and eradicates biofilm of C. glabrata and its clinical isolates. • GR inactivates the hydrolytic enzymes in extracellular matrix. • GR mediates C. glabrata apoptosis by interfering with multiple signaling pathways.


Assuntos
Biofilmes , Candida glabrata , Monoterpenos Acíclicos , Antifúngicos/farmacologia , Candida , Testes de Sensibilidade Microbiana
12.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206015

RESUMO

New polymer-bioactive compound systems were obtained by immobilization of triazole derivatives onto grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole. For preparation of bioactive compound, two new types of heterocyclic thio-derivatives with different substituents were combined in a single molecule to increase the selectivity of the biological action. The 5-aryl-amino-1,3,4 thiadiazole and 5-mercapto-1,2,4-triazole derivatives, each containing 2-mercapto-benzoxazole nucleus, were prepared by an intramolecular cyclization of thiosemicarbazides-1,4 disubstituted in acidic and basic medium. The structures of the new bioactive compounds were confirmed by elemental and spectral analysis (FT-IR and 1H-NMR). The antimicrobial activity of 1,3,4 thiadiazoles and 1,2,4 triazoles was tested on gram-positive and gram-negative bacteria. The triazole compound was chosen to be immobilized onto polymeric particles by adsorption. The Langmuir, Freundlich, and Dubinin-Radushkevich adsorption isotherm were used to describe the adsorption equilibrium. Also, the pseudo-first and pseudo-second models were used to elucidate the adsorption mechanism of triazole onto grafted copolymer based on N-vinylimidazole and gellan (PG copolymer) and grafted copolymers carrying betaine units (PGB1 copolymer). In vitro release studies have shown that the release mechanism of triazole from PG and PGB1 copolymers is characteristic of an anomalous transport mechanism.


Assuntos
Antibacterianos/síntese química , Betaína/química , Polissacarídeos Bacterianos/química , Triazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus cereus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Ciclização , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Salmonella enteritidis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Triazóis/química , Triazóis/farmacologia
13.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198771

RESUMO

This study investigated within-plant variability of the main bioactive compounds in rosemary (Rosmarinus officinalis L.). Volatile terpenes, including the enantiomeric distribution of monoterpenes, and phenols were analyzed in young and mature foliar, cortical and xylem tissues. In addition, antimicrobial activity of rosmarinic acid and selected terpenes was evaluated against two rosemary pathogens, Alternaria alternata and Pseudomonas viridiflava. Data showed that total concentration and relative contents of terpenes changed in relation to tissue source and age. Their highest total concentration was observed in the young leaves, followed by mature leaves, cortical and xylem tissues. Rosmarinic acid and carnosic acid contents did not show significant differences between leaf tissues of different ages, while young and mature samples showed variations in the content of four flavonoids. These results are useful for a more targeted harvesting of rosemary plants, in order to produce high-quality essential oils and phenolic extracts. Microbial tests showed that several terpenes and rosmarinic acid significantly inhibited the growth of typical rosemary pathogens. Overall, results on antimicrobial activity suggest the potential application of these natural compounds as biochemical markers in breeding programs aimed to select new chemotypes less susceptible to pathogen attacks, and as eco-friendly chemical alternatives to synthetic pesticides.


Assuntos
Anti-Infecciosos/farmacologia , Fenóis/farmacologia , Rosmarinus/química , Terpenos/farmacologia , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Anti-Infecciosos/química , Cinamatos/farmacologia , Depsídeos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Especificidade de Órgãos , Fenóis/química , Pseudomonas/efeitos dos fármacos , Pseudomonas/crescimento & desenvolvimento , Rosmarinus/microbiologia , Terpenos/química
14.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198776

RESUMO

In this paper, peptide conjugates were designed and synthesized by incorporating the antimicrobial undecapeptide BP16 at the C- or N-terminus of the plant defense elicitor peptide flg15, leading to BP358 and BP359, respectively. The evaluation of their in vitro activity against six plant pathogenic bacteria revealed that BP358 displayed MIC values between 1.6 and 12.5 µM, being more active than flg15, BP16, BP359, and an equimolar mixture of BP16 and flg15. Moreover, BP358 was neither hemolytic nor toxic to tobacco leaves. BP358 triggered the overexpression of 6 out of the 11 plant defense-related genes tested. Interestingly, BP358 inhibited Erwinia amylovora infections in pear plants, showing slightly higher efficacy than the mixture of BP16 and flg15, and both treatments were as effective as the antibiotic kasugamycin. Thus, the bifunctional peptide conjugate BP358 is a promising agent to control fire blight and possibly other plant bacterial diseases.


Assuntos
Erwinia amylovora/crescimento & desenvolvimento , Proteínas Citotóxicas Formadoras de Poros/síntese química , Pyrus/crescimento & desenvolvimento , Erwinia amylovora/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Pyrus/microbiologia
15.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206444

RESUMO

The alarming raise of multi-drug resistance among human microbial pathogens makes the development of novel therapeutics a priority task. In contrast to conventional antibiotics, antimicrobial peptides (AMPs), besides evoking a broad spectrum of activity against microorganisms, could offer additional benefits, such as the ability to neutralize toxins, modulate inflammatory response, eradicate bacterial and fungal biofilms or prevent their development. The latter properties are of special interest, as most antibiotics available on the market have limited ability to diffuse through rigid structures of biofilms. Lipidation of AMPs is considered as an effective approach for enhancement of their antimicrobial potential and in vivo stability; however, it could also have undesired impact on selectivity, solubility or the aggregation state of the modified peptides. In the present work, we describe the results of structural modifications of compounds designed based on cationic antimicrobial peptides DK5 and CAR-PEG-DK5, derivatized at their N-terminal part with fatty acids with different lengths of carbon chain. The proposed modifications substantially improved antimicrobial properties of the final compounds and their effectiveness in inhibition of biofilm development as well as eradication of pre-formed 24 h old biofilms of Candida albicans and Staphylococcus aureus. The most active compounds (C5-DK5, C12-DK5 and C12-CAR-PEG-DK5) were also potent against multi-drug resistant Staphylococcus aureus USA300 strain and clinical isolates of Pseudomonas aeruginosa. Both experimental and in silico methods revealed strong correlation between the length of fatty acid attached to the peptides and their final membranolytic properties, tendency to self-assemble and cytotoxicity.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Estabilidade de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Análise Espectral , Relação Estrutura-Atividade , Termodinâmica
16.
BMJ Case Rep ; 14(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210697

RESUMO

A 10-year-old boy treated for alkali injury with multiple interventions presented with a perforated corneal ulcer with clinically suspected bacterial aetiology. Cornea scraping and tissue adhesive application were planned. During surgery, an eyelash was found embedded at the perforated site. Gram staining of corneal scraping revealed the presence of Gram-positive bacilli on the first day which later was identified as Turicella otitidis with culture followed by VITEK V.2.0 (Biomerieux) identification. The bacterium was found to be sensitive to amikacin, ciprofloxacin, cefazolin, gatifloxacin, moxifloxacin, ofloxacin and vancomycin antibiotics as per Clinical and Laboratory Standards Institute guidelines. Coryneform bacteria is a rare cause of keratitis, and this is the first reported case of microbial keratitis caused by one of the rare corynebacterium species T. otitidis to the best of our knowledge. Literature search does not reveal any specific ocular features typical to this organism. This case supports the growing evidence for pathogenicity of T. otitidis in ocular samples. This study demonstrates the utility of VITEK for the identification of rare pathogen and may facilitate the use of certain antibiotics in the treatment regimen of T. otitidis infections.


Assuntos
Infecções Oculares Bacterianas , Ceratite , Antibacterianos/uso terapêutico , Criança , Corynebacterium , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Masculino , Testes de Sensibilidade Microbiana , Ofloxacino
17.
J Nanosci Nanotechnol ; 21(12): 5945-5959, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229790

RESUMO

Zinc oxide nanoparticles were synthesized using different surfactants such as SDS, CTAB, Triton X-100, PVP K-30 and ethylene glycol. ZnO NPs were tested for antibacterial activity before and after calcination against different micro-organisms like E. coli and P. aeruginosa (Gram negative) as well as S. aureus and B. subtilis (Gram positive). Antibacterial activity was observed in SDScapped ZnO NPs only against B. subtilis. Antibacterial activity of ZnO-capped SDS was tested in a concentration range 0.625-10 mg/mL. Increased antibacterial activity was observed before calcination as compared to after calcination. Minimum concentration at which uncalcinated as well as calcinated SDS-capped ZnO NPs show antibacterial activity is 2.5 mg/mL and 5 mg/mL respectively. Non-antibacterial nature of ZnO NPs highlights its further use in drug delivery due to its inert nature, enhanced efficacy in association with therapeutic drugs as well as easy disposal.


Assuntos
Nanopartículas , Óxido de Zinco , Antibacterianos/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Tensoativos/farmacologia , Óxido de Zinco/farmacologia
18.
BMJ Case Rep ; 14(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230047

RESUMO

Renal transplant recipients are at risk for opportunistic infections due to their immunosuppressed state. We describe the case of a 59-year-old renal transplant recipient who presented with sepsis and bilateral pulmonary emboli due to Candida parapsilosis She was treated with intravenous caspofungin and had a transoesophageal echocardiogram, which revealed vegetations on her pacemaker leads. She then underwent surgery to replace her pacemaker; however, her blood cultures remained positive for C. parapsilosis postoperatively. Her antifungal was switched to liposomal amphotericin B and flucytosine for 6 weeks, which yielded sterile blood cultures, and she was then initiated on lifelong fluconazole. Her recovery was complicated by tacrolimus toxicity 1 month after discharge due to fluconazole-induced CYP3A inhibition.


Assuntos
Fungemia , Transplante de Rim , Marca-Passo Artificial , Antifúngicos/uso terapêutico , Candida parapsilosis , Feminino , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Humanos , Transplante de Rim/efeitos adversos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
19.
Molecules ; 26(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198510

RESUMO

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8-45.6 M-1 and enthalpy change values up to -4 kJ·M-1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cafeína/farmacologia , Compostos Heterocíclicos/química , Pentoxifilina/farmacologia , Antibacterianos/química , Bactérias/crescimento & desenvolvimento , Cafeína/química , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacologia , Interações Medicamentosas , Testes de Sensibilidade Microbiana , Pentoxifilina/química , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia
20.
Molecules ; 26(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198596

RESUMO

Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) bacteria represent major infectious threats in the hospital environment due to their wide distribution, opportunistic behavior, and increasing antibiotic resistance. This study reports on the deposition of polyvinylpyrrolidone/antibiotic/isoflavonoid thin films by the matrix-assisted pulsed laser evaporation (MAPLE) method as anti-adhesion barrier coatings, on biomedical surfaces for improved resistance to microbial colonization. The thin films were characterized by Fourier transform infrared spectroscopy, infrared microscopy, and scanning electron microscopy. In vitro biological assay tests were performed to evaluate the influence of the thin films on the development of biofilms formed by Gram-positive and Gram-negative bacterial strains. In vitro biocompatibility tests were assessed on human endothelial cells examined for up to five days of incubation, via qualitative and quantitative methods. The results of this study revealed that the laser-fabricated coatings are biocompatible and resistant to microbial colonization and biofilm formation, making them successful candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Flavonoides/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Biofilmes/crescimento & desenvolvimento , Materiais Revestidos Biocompatíveis/química , Flavonoides/química , Lasers/normas , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Propriedades de Superfície
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